PROJECT SUMMARY Project Title: Next-Generation Antibody Discovery and Development Technology Organization: GigaGen Inc. PI: David S. Johnson, Ph.D. Despite an enormous investment in novel therapies, cancer still accounts for 25% of US deaths, killing >1500 people every day. For example, only 25% of pancreatic cancer patients and 17% of lung cancer patients survive one year after diagnosis. Additionally, oncology treatments cost $127 billion per year in the US, and are expected to grow at 27% per year through 2020. Monoclonal antibodies (mAbs) are now the biological agents of choice for cancer therapy. Three of the top six grossing therapeutics worldwide (bevacizumab, rituximab, and trastuzumab) are oncology mAbs. Today, most mAb discovery programs use either some flavor of single chain variable fragment (scFv) display or mouse immunization followed by hybridoma isolation. Display technologies like phage display have tremendous ease of use, which enables R&D programs to screen through billions of antibodies in parallel. Unlike conventional phage display technologies, mouse immunizations produce fully natural antibodies, which are often easier to develop than antibodies discovered through display. Though display and mouse immunizations have produced breakthrough therapeutic antibodies, R&D programs are always looking for faster, deeper, and more efficient antibody technologies. The Specific Aim of this IMAT Phase II SBIR project is to develop GigaLink?, a next-generation high-throughput molecular technology for discovery and development of oncology drugs from mammalian B cell repertoires. GigaLink? is the only technology that uses primary B cells to make millions- to billions-diverse DNA libraries of antibodies, and then expresses the DNA libraries as protein for affinity screening and antigen discovery. As a DNA-based technology, GigaLink? uniquely enables massively parallel antibody screening, engineering, and development. A successful IMAT Phase II SBIR project will show that the GigaLink? antibody R&D platform can help our customers understand basic tumor immunology and discover and develop therapeutic antibody candidates. We will use the profits from GigaLink? service revenues plus venture capital to build our own internal programs for oncology therapeutic antibody discovery.